Natural selection on EPAS1 (HIF2 ) associated with low hemoglobin concentration in Tibetan highlanders

In a separate cohort of Tibetans residing at 4,200 m, we identified 31 EPAS1 SNPs in high linkage disequilibrium that correlated significantly with hemoglobin concentration

C. M. Beall; G. L. Cavalleri; L. Deng; R. C. Elston; Y. Gao; J. Knight; C. Li; J. C. Li; Y. Liang; M. McCormack; H. E. Montgomery; H. Pan; P. A. Robbins; K. V. Shianna; S. C. Tam; N. Tsering; K. R. Veeramah; W. Wang; P. Wangdui; M. E. Weale; Y. Xu; Z. Xu; L. Yang; M. J. Zaman; C. Zeng; L. Zhang; X. Zhang; P. Zhaxi; Y. T. Zheng


Scholarcy highlights

  • We postulated that any marked differences in SNP frequencies between the Yunnan Tibetan and the HapMap Han populations could reflect a history of divergent selection on functional variation that contributes to increased survival at high altitude. Of the 502,722 SNPs that were included in the analysis, eight SNPs emerged as having genome-wide significance, all located within 235 kb on chromosome 2
  • The SNPs lie between 366 bp and 235 kb downstream of EPAS1 but, as we show below, the region of high linkage disequilibrium extends into EPAS1 itself
  • As large genome-wide association studies of the determinants of hemoglobin concentration in other populations at low altitude have failed to detect a signal associated with EPAS1, our results suggest either that there is a genetic variant that is quite specific to the Tibetan population or that the variant is quite specific to moderating hemoglobin concentration only under conditions of high altitude
  • Such specificity of effect in relation to Tibetan highlanders is in keeping with a model of selection pressure on EPAS1 under the stress of high-altitude hypoxia
  • 49 had a minor allele frequency ≥5%, and were amenable to regression analysis that identified 31 SNP sites significantly associated with hemoglobin concentration
  • It is possible that the Andean and Tibetan populations have developed different genetic adaptations to the hypoxia of high altitude given the differences in physiology that are known to exist between these populations
  • Candidate gene association analysis of EPAS1 SNP genotype with hemoglobin concentration phenotype was performed separately in the two Tibet Autonomous Region samples

Need more features? Save interactive summary cards to your Scholarcy Library.